The University of Chicago Medicine (UC) proposes to join the Early Therapeutics-Clinical Trials Network (ET-CTN). The early development of novel anticancer agents requires innovative approaches to adapt to the changing environment of cancer therapeutics development. Standards of care for advanced metastatic solid tumors have improved, rapid technological advances in molecular biotechnology have brought new tools and therapeutic strategies, and advances in information technology enable collection and analysis of larger datasets and more efficient inter-institutional collaboration. But fundamental principles of drug development remain essential to improving cancer care. Our center proposes to join the ET-CTN as a highly collaborative site, experienced in team science, with specific expertise in: innovative clinical trial design and quantitative analysis methods, application and validation of biomarkers in early therapeutics development, and pharmacogenomics of cancer therapeutics. Our site brings the resources and expertise of our Comprehensive Cancer Center, an early therapeutics development team with extensive experience, and a team of clinical oncologists with both disease-specific patient care and research expertise. Our leadership have already conducted effective team science within the NCI Investigational Drug Steering Committee and Cooperative Groups as well as in the NIGMS-sponsored Pharmacogenomics Research Network. UC team members will participate actively on projects led by the collaborative groups in the network, offering their relevant expertise. UC will lead efforts in pharmacogenomics, biomarker validation, and design and conduct of novel clinical trials. We also plan to implement computational modeling and simulation strategies to: 1) improve trial designs, 2) identify the range of doses of new agents to be tested in later trials, 3) to demonstrate relevance of candidate biomarkers for further development, and 4) support strategic decision-making by the ET-CTN on which agents and combinations are most likely to have the intended impact on clinical care in later phases of drug development.